This proposal is for a 5-year competing renewal of the University of Washington (UW) Superfund Basic Research Program Project. The theme of this program is that biomarkers measured in accessible tissues are predictive of: a) toxicant exposures;b) early indicators of damage;and/or c) unusual susceptibility to toxic agents that commonly occur at Superfund sites. The proposed UW Program includes 5 research projects (3 biomedical, 2 non-biomedical [ecotoxicology, bioremediation]), 2 of which are new (both biomedical). The program will focus most intensively on biomarker applications for investigations of adverse effects to human health and the environment from neurotoxic chemicals, primarily metals and pesticides. Collectively, these projects will develop and validate biomarkers for: elucidating underlying neurotoxicity mechanisms in humans and animal models;identifying early-stage neurologic disease processes in humans;characterizing dose-response relations for selected neurotoxicants with neurologic disease risk, severity, and progression, using PS as a model outcome;and, for implementing phytoremediation techniques. The research projects include studies of: 1) animal models of susceptibility to organophosphate pesticides, with applications to pesticide-exposed farmworkers and to persons affected with Parkinson's disease;2) metals and Parkinsonism among professional welders;3) proteomic markers of metal-induced PS;4) sub-lethal neurotoxic effects of metals and pesticides in free-living Coho salmon;and, 5) phytoremediation methods for organic solvents and pesticides. The Administrative Core will oversee all budgetary and reporting aspects of the Program, and will foster multidisciplinary interactions among projects and cores. The Functional Genomics and Bioinformatics Core will provide extensive molecular biology laboratory and data analysis support to all research projects. The Research Translation Core will ensure timely and appropriate communication of our research findings to relevant stakeholders, including government agencies, community groups, and the private sector. ADMINISTRATIVE CORE (Checkoway) Description (provided by applicant) The Administrative Core provides overall direction and administrative support to the entire UW SBRP Program. This core is directed by Dr. Harvey Checkoway, who is the Program Director. Dr. Checkoway is assisted by the Deputy Director, Dr. Evan Gallagher, the Program Manager, Ms. Tran, and the Program Coordinator, Ms. Saucier. Administrative and scientific advice will be provided by an Internal Executive Committee, composed of Project and Core Directors, and the External Science Advisory Board that includes accomplished environmental scientists from academia and Federal government agencies. The essential functions of the Administrative Core are to: 1) plan and coordinate research activities, including the integration of cross-disciplinary collaborations;2) coordinate the activities of research projects with the Research Translation and the Functional Genomics and Bioinformatics Cores;3) ensure efficient management of budgets and personnel matters;and, 4) oversee preparation of non-competing grant renewal applications. In addition, the Administrative Core will work closely with the Research Translation Core to implement a structured program of information dissemination of research findings to NIEHS administrators and scientists, regional and federal government administrators and scientists, community residents, and appropriate representatives from the private sector.